单细胞测序分析喉癌及其微环境代谢相关靶基因

doi:10.6040/j.issn.1673-3770.0.2021.542

摘要/Abstract

摘要： 目的利用单细胞测序技术寻找喉癌细胞糖酵解和谷氨酰胺代谢相关中小分子靶向药物可能的靶基因。方法利用R语言对既往单细胞测序的结果重分析,对细胞进行TSNE分类,对代谢相关基因在喉癌各细胞亚群中的表达进行分析。结果喉癌细胞糖酵解过程中可能成为小分子代谢药物作用靶点的基因包括:葡萄糖转运蛋白、己糖激酶、丙酮酸激酶;谷氨酰胺分解代谢中可能成为药物作用的靶基因包括:谷氨酰胺转运蛋白、谷氨酰胺酶、谷氨酸脱氢酶1、苹果酸脱氢酶、乳酸脱氢酶、异柠檬酸脱氢酶2。结论喉癌细胞中存在与糖酵解和谷氨酰胺代谢相关的基因靶点,可以作为药物研发的方向。

关键词: 糖酵解, 谷氨酰胺代谢, 喉癌, 单细胞测序

Abstract: Objective Single cell sequence was used to find the possible targets of metabolism related small molecular drugs targeted on laryngeal cancer glycolysis and glutaminolysis. Methods R language reanalyzed the results of single cell sequence, cells were classified with TSNE and metabolic related genes expression were measured. Results The target genes of glycolysis in laryngeal cancer include glucose transporters, hexokinase, pyruvate kinase. Genes in glutaminolysis include: Na⁺ coupled transporter for glutamine, glutaminase, glutamate dehydrogenase 1, malate dehydrogenase, lactate dehydrogenase, isocitrate hydrogenase 2. Conclusion In the process of glycolysis and glutaminolysis exist targets for metabolic drugs and this may be used for the develop of new target drugs.

Key words: Glycolysis, Glutaminolysis, Laryngeal cancer, Single cell sequence

中图分类号:

R739.6

徐翀,王晓亭,易红良. 单细胞测序分析喉癌及其微环境代谢相关靶基因[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 33-38.

XU Chong, WANG Xiaoting, YI Hongliang. Single-cell sequencing analysis of laryngeal cancer and its microenvironmental metabolism-related target genes[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(2): 33-38.

参考文献

[1] Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi:10.3322/caac.21338
[2] Solomon B, Young RJ, Rischin D. Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments[J]. Semin Cancer Biol, 2018, 52(Pt 2): 228-240. doi:10.1016/j.semcancer.2018.01.008
[3] Barupal DK, Pinkerton KE, Hood C, et al. Environmental tobacco smoke alters metabolic systems in adult rats[J]. Chem Res Toxicol, 2016, 29(11): 1818-1827. doi:10.1021/acs.chemrestox.6b00187
[4] Vanhove K, Graulus GJ, Mesotten L, et al. The metabolic landscape of lung cancer: new insights in a disturbed glucose metabolism[J]. Front Oncol, 2019, 9: 1215. doi:10.3389/fonc.2019.01215
[5] Dang CV. Links between metabolism and cancer[J]. Genes Dev, 2012, 26(9): 877-890. doi:10.1101/gad.189365.112
[6] Vanhove K, Derveaux E, Graulus GJ, et al. Glutamine addiction and therapeutic strategies in lung cancer[J]. Int J Mol Sci, 2019, 20(2): E252. doi:10.3390/ijms20020252
[7] Zhang J, Pavlova NN, Thompson CB. Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine[J]. EMBO J, 2017, 36(10): 1302-1315. doi:10.15252/embj.201696151
[8] Jin L, Alesi GN, Kang S. Glutaminolysis as a target for cancer therapy[J]. Oncogene, 2016, 35(28): 3619-3625. doi:10.1038/onc.2015.447
[9] Wang JB, Erickson JW, Fuji R, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation[J]. Cancer Cell, 2010, 18(3): 207-219. doi:10.1016/j.ccr.2010.08.009
[10] Song L, Zhang S, Yu S, et al. Cellular heterogeneity landscape in laryngeal squamous cell carcinoma[J]. Int J Cancer, 2020, 147(10): 2879-2890. doi:10.1002/ijc.33192
[11] Luo XM, Zhou SH, Fan J. Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma[J]. J Int Med Res, 2010, 38(6): 1885-1892. doi:10.1177/147323001003800601
[12] Shen LF, Zhao X, Zhou SH, et al. In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT[J]. Oncotarget, 2017, 8(21): 34709-34726. doi:10.18632/oncotarget.16671
[13] Patra KC, Wang Q, Bhaskar PT, et al. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer[J]. Cancer Cell, 2013, 24(2): 213-228. doi:10.1016/j.ccr.2013.06.014
[14] Gao Y, Xu D, Yu G, et al. Overexpression of metabolic markers HK₁ and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer[J]. Int J Clin Exp Pathol, 2015, 8(8): 9264-9271
[15] Mor I, Cheung EC, Vousden KH. Control of glycolysis through regulation of PFK1: old friends and recent additions[J]. Cold Spring Harb Symp Quant Biol, 2011, 76: 211-216. doi:10.1101/sqb.2011.76.010868
[16] Webb BA, Forouhar F, Szu FE, et al. Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations[J]. Nature, 2015, 523(7558): 111-114. doi:10.1038/nature14405
[17] Lee JH, Liu R, Li J, et al. Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis[J]. Nat Commun, 2017, 8(1): 949. doi:10.1038/s41467-017-00906-9
[18] Dey P, Son JY, Kundu A, et al. Knockdown of pyruvate kinase M2 inhibits cell proliferation, metabolism, and migration in renal cell carcinoma[J]. Int J Mol Sci, 2019, 20(22): E5622. doi:10.3390/ijms20225622
[19] James AD, Richardson DA, Oh IW, et al. Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2(PKM2)[J]. Br J Cancer, 2020, 122(2): 266-278. doi:10.1038/s41416-019-0675-3
[20] Dey P, Kundu A, Sachan, et al. PKM2 knockdown induces autophagic cell death via AKT/mTOR pathway in human prostate cancer cells[J]. Cell Physiol Biochem, 2019, 52(6): 1535-1552. doi:10.33594/000000107
[21] 刘晓晓. PKM2和HIF-1α在喉鳞状细胞癌中的表达及意义[D]. 石家庄: 河北医科大学, 2015.
[22] Zhang Z, Liu R, Shuai Y, et al. ASCT2(SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma[J]. Br J Cancer, 2020, 122(1): 82-93. doi:10.1038/s41416-019-0637-9
[23] Lukey MJ, Greene KS, Erickson JW, et al. The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy[J]. Nat Commun, 2016, 7: 11321. doi:10.1038/ncomms11321
[24] Zhang J, Mao S, Guo Y, et al. Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer[J]. Biosci Rep, 2019, 39(6): BSR20181826. doi:10.1042/BSR20181826
[25] Momcilovic M, Bailey ST, Lee JT, et al. Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer[J]. Cell Rep, 2017, 18(3): 601-610. doi:10.1016/j.celrep.2016.12.061
[26] Craze ML, El-Ansari R, Aleskandarany MA, et al. Glutamate dehydrogenase(GLUD1)expression in breast cancer[J]. Breast Cancer Res Treat, 2019, 174(1): 79-91. doi:10.1007/s10549-018-5060-z
[27] New M, Van Acker T, Sakamaki JI, et al. MDH1 and MPP₇ regulate autophagy in pancreatic ductal adenocarcinoma[J]. Cancer Res, 2019, 79(8): 1884-1898. doi:10.1158/0008-5472.CAN-18-2553
[28] Lu YX, Ju HQ, Liu ZX, et al. ME1 regulates NADPH homeostasis to promote gastric cancer growth and metastasis[J]. Cancer Res, 2018, 78(8): 1972-1985. doi:10.1158/0008-5472.CAN-17-3155
[29] Liu C, Cao J, Lin SC, et al. Malic enzyme 1 indicates worse prognosis in breast cancer and promotes metastasis by manipulating reactive oxygen species[J]. Onco Targets Ther, 2020, 13: 8735-8747. doi:10.2147/OTT.S256970
[30] Zhu YH, Gu L, Lin X, et al. Dynamic regulation of ME1 phosphorylation and acetylation affects lipid metabolism and colorectal tumorigenesis[J]. Mol Cell, 2020, 77(1): 138-149.e5. doi:10.1016/j.molcel.2019.10.015
[31] Guo EL, Guo LH, An CM, et al. Prognostic significance of lactate dehydrogenase in patients undergoing surgical resection for laryngeal squamous cell carcinoma[J]. Cancer Control, 2020, 27(1): 1073274820978795. doi:10.1177/1073274820978795
[32] Li JJ, He Y, Tan ZQ, et al. Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer[J]. Theranostics, 2018, 8(15): 4050-4061. doi:10.7150/thno.21524
[33] Dang L, Yen K, Attar EC. IDH mutations in cancer and progress toward development of targeted therapeutics[J]. Ann Oncol, 2016, 27(4): 599-608. doi:10.1093/annonc/mdw013

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